As many individuals once treated for childhood cancer progress into adulthood, clinical and epidemiologic research is now focusing on an array of long-term effects from cancer treatment to characterize and understand the "consequences of cure". There is evidence to indicate that childhood cancer survivors (CCS) are at increased risk for the metabolic syndrome (MS). The syndrome is composed of obesity, insulin resistance, dyslipidemia and hypertension, and is a predictor of type 2 diabetes and cardiovascular disease. In healthy populations obesity has a central role in the development of the MS, however, it is conceivable that in CCS additional mechanisms other than obesity (e.g. endocrine abnormalities, exposure to radiation and antineoplastic agents) may play a critical role in the development of MS. The major objective of this proposal is to evaluate the relation between insulin resistance (by euglycemic insulin clamp), growth hormone deficiency and other mediators of insulin resistance, with the development of MS and cardiovascular risk early in life, before the relations between the components become complex and disease develops. We propose to study a sample of children and adolescents age 9-18 years, who survived childhood cancer for >5 years after diagnosis, and their healthy siblings, who will participate in a 2 day clinical evaluation. Specific aims are: 1) to determine the prevalence of MS in CCS and compare to healthy controls similar in age and gender distribution, 2) to assess the association of insulin resistance with other components of MS and with early signs of cardiovascular changes, and 3) to assess the relation between obesity and insulin resistance with growth hormone secretion,^adipokines and inflammatory mediators; 4) to evaluate health behaviors related to prevention of cardiovascular disease, diabetes, and obesity. This proposal addresses the need for clinical research focused on newly identified adverse effects of childhood cancer and its treatment, particularly for preventable/modifiable conditions, and will provide new data on potential etiologic factors and avenues for intervention. [unreadable] [unreadable]